Wallenius V, Elias E, Bergstrom G M L, Zetterberg H, Behre C J
Department of Gastrosurgical Research, Sahlgrenska Academy at Sahlgrenska University Hospital, Gothenburg, Sweden.
Exp Clin Endocrinol Diabetes. 2011 Feb;119(2):75-80. doi: 10.1055/s-0030-1265212. Epub 2010 Nov 22.
The lipocalins retinol-binding protein (RBP)-4, lipocalin-2 and lipocalin-type prostaglandin D-synthase (L-PGDS) have been suggested to mediate obesity-associated insulin resistance and other metabolic co-morbidities. The role of lipocalins is however controversial and it is unclear whether they have a physiological role in regulation of insulin sensitivity and metabolic function in clinically healthy humans. Therefore, we examined the correlations between serum levels of RBP-4, L-PGDS and lipocalin-2 and insulin sensitivity and other metabolic parameters in non-diabetic subjects selected to display variations in insulin sensitivity. 100 clinically healthy 58-year-old Swedish men were selected by stratified sampling among 818 screened subjects to represent quintiles of varying degrees of insulin sensitivity. Insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp method. Serum levels of lipocalins and cytokines were determined using antibody-based techniques. Serum lipids were measured by standardized laboratory methods. None of the measured lipocalins showed any correlations with insulin sensitivity. However, we found that lipocalin-2 and L-PGDS were correlated with each other, but not with RBP-4. Lipocalin-2 and L-PGDS were positively correlated with soluble TNF- receptors 1 and 2 and negatively with alcohol consumption and serum HDL. Further, lipocalin-2 was correlated with interleukin-6 whereas RBP-4 was negatively correlated with TNF-α. □These results suggest that RBP-4, lipocalin-2 and L-PGDS do not regulate insulin sensitivity in healthy men. Rather the expression levels of lipocalin-2 and L-PGDS, but not RBP-4, seemed to reflect inflammatory activity and were inversely correlated with alcohol intake and serum HDL levels.
有人提出,视黄醇结合蛋白(RBP)-4、2型载脂蛋白和脂联素型前列腺素D合成酶(L-PGDS)介导肥胖相关的胰岛素抵抗和其他代谢合并症。然而,脂联素的作用存在争议,尚不清楚它们在临床健康人群的胰岛素敏感性和代谢功能调节中是否具有生理作用。因此,我们研究了在选择的胰岛素敏感性存在差异的非糖尿病受试者中,RBP-4、L-PGDS和2型载脂蛋白的血清水平与胰岛素敏感性及其他代谢参数之间的相关性。通过分层抽样从818名筛查对象中选取了100名临床健康的58岁瑞典男性,以代表不同程度胰岛素敏感性的五分位数。采用正常血糖高胰岛素钳夹法测量胰岛素敏感性。使用基于抗体的技术测定脂联素和细胞因子的血清水平。通过标准化实验室方法测量血脂。所测的脂联素均与胰岛素敏感性无任何相关性。然而,我们发现2型载脂蛋白与L-PGDS相互相关,但与RBP-4不相关。2型载脂蛋白和L-PGDS与可溶性肿瘤坏死因子受体1和2呈正相关,与饮酒量和血清高密度脂蛋白呈负相关。此外,2型载脂蛋白与白细胞介素-6相关,而RBP-4与肿瘤坏死因子-α呈负相关。□这些结果表明,RBP-4、2型载脂蛋白和L-PGDS在健康男性中不调节胰岛素敏感性。相反,2型载脂蛋白和L-PGDS的表达水平(而非RBP-4)似乎反映了炎症活动,且与酒精摄入量和血清高密度脂蛋白水平呈负相关。